Original article

Cancer Immunology, Immunotherapy

, Volume 62, Issue 1, pp 39-49

First online:

Lenalidomide enhances anti-myeloma cellular immunity

  • Katarina LuptakovaAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center Email author 
  • , Jacalyn RosenblattAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center
  • , Brett GlotzbeckerAffiliated withDana Farber Cancer Institute
  • , Heidi MillsAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center
  • , Dina StroopinskyAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center
  • , Turner KufeAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center
  • , Baldev VasirAffiliated withDana Farber Cancer Institute
  • , Jon ArnasonAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center
  • , Dimitri TzachanisAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center
    • , Jeffrey I. ZwickerAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center
    • , Robin M. JoyceAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center
    • , James D. LevineAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center
    • , Kenneth C. AndersonAffiliated withDana Farber Cancer Institute
    • , Donald KufeAffiliated withDana Farber Cancer Institute
    • , David AviganAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center

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Abstract

Lenalidomide is an effective therapeutic agent for multiple myeloma that exhibits immunomodulatory properties including the activation of T and NK cells. The use of lenalidomide to reverse tumor-mediated immune suppression and amplify myeloma-specific immunity is currently being explored. In the present study, we examined the effect of lenalidomide on T-cell activation and its ability to amplify responses to a dendritic cell-based myeloma vaccine. We demonstrate that exposure to lenalidomide in the context of T-cell expansion with direct ligation of CD3/CD28 complex results in polarization toward a Th1 phenotype characterized by increased IFN-γ, but not IL-10 expression. In vitro exposure to lenalidomide resulted in decreased levels of regulatory T cells and a decrease in T-cell expression of the inhibitory marker, PD-1. Lenalidomide also enhanced T-cell proliferative responses to allogeneic DCs. Most significantly, lenalidomide treatment potentiated responses to the dendritic cell/myeloma fusion vaccine, which were characterized by increased production of inflammatory cytokines and increased cytotoxic lymphocyte-mediated lysis of autologous myeloma targets. These findings indicate that lenalidomide enhances the immunologic milieu in patients with myeloma by promoting T-cell proliferation and suppressing inhibitory factors, and thereby augmenting responses to a myeloma-specific tumor vaccine.

Keywords

Lenalidomide Multiple myeloma Dendritic cell vaccine PD-1